Scutellarin is effective in improving cerebral blood circulation, enhancing cerebral blood flow, reducing blood viscosity, anti-platelet aggregation, and the like. Scutellarin is widely applied in clinical treatment, and is mainly applied to a cardiovascular or cerebrovascular disease, such as sequelae of paralysis caused by occlusive cerebrovascular disease, coronary heart disease, and angina pectoris. Scutellarin has a significant efficacy in the treatment of a cardiovascular or cerebrovascular disease, rheumatic arthritis, stroke sequelae and the like (Tang Yuping, Li Nianguang, Duan Jinao, Scutellarein derivative as well as preparation method and application thereof [P]. Jiangsu: CN101891728A, 2010-11-24.). In addition, breviscapine is also clinically useful in the treatment of a renal disease such as nephritic syndrome, diabetic nephropathy and chronic glomerulonephritis; a hepatic disease such as antituberculosis drug-induced liver injury, acute jaundice hepatitis, chronic hepatitis and refractory ascites due to cirrhosis; acute exacerbation of chronic obstructive pulmonary disease with hypoxemia; a diabetic chronic complication such as diabetic peripheral neuropathy and diabetic foot; an ocular disease such as commotio retinae, ischemic optic neuropathy, and ocular central serous chorioretinopathy; and a disease such as sudden deafness and fetal growth restriction (Sun Hua, Song Yi, Extending application of breviscapine in clinic [J]. ASIA-PACIFIC TRADITIONAL MEDICINE, 2013, 05:63-64.).
Since the purification process was not well-established previously, breviscapine is generally used as a crude drug in the clinical treatment of diseases. The problem concerning the administration of breviscapine resides in that breviscapine itself is a mixture of scutellarin, scutellarin isomer-isoscutellarin, and others, and has complex components, and therefore there are some difficulties in quality control. Scutellarin is the principal component breviscapine, and is resulted from technical development. However, scutellarin has a poor oral absorption, and a low oral availability.
Scutellarin aglycone is the hydrolysis product of scutellarin (Liu Jianming, Xiong Yuqing, Advances in studies on pharmacokinetics of scutellarin and scutellarein [J]. CHINA JOURNAL OF CHINESE MATERIA MEDICA, 2009, 24:3165-3168.), also called scutellarein, CAS NO. 529-53-3, with a molecular formula of C15H10O6, and a molecular weight of 286.2.
With the development in purification and isolation techniques as well as detection techniques, in combination with the researches and discoveries on scutellarin and its aglycone, it has been found that scutellarin aglycone has a higher permeability in gastrointestinal tract than scutellarin, and has an oral absorption that is about 3-fold of that of scutellarin. Che Qingming et al., studied the intragastric administration of an equal amount of scutellarin aglycone and scutellarin to rats, respectively, and showed that oral administration of scutellarin aglycone facilitated absorption, and scutellarin aglycone was metabolically stable relative to scutellarin, and had a relative bioavailability of 301.8% (Chen Qingming, Chen Ying, Pan Liyi, He Hong, Scutellarein's pharmacokinetics in rats [J]. CHINESE JOURNAL OF NEW DRUGS, 2006, 18: 1557-1561.). Che Qingming et al. also found that after oral administration, seutellarin aglycone was mainly converted to the effective ingredient (i.e. scutellarin) of Erigeron breviscapus injection in vivo, and its blood distribution was close to that of Erigeron breviscapus injection (Chen Qingming, Pan Liyi, Chen Ying, He Hong, Study on Pharmacokinetics of Scutellarein in Rats [J], CHINESE PHARMACEUTICAL JOURNAL, 2007, 18: 1418-1421.). In other words, seutellarin aglycone almost has the same pharmacological activity as scutellarin. Lv et al. studied the pharmacokinetics of scutellarin liposomes in brain tissues, and based on the existing research results, it shows that scutellarin could cross the blood brain barrier and was distributed in brain tissues (Int J Pharm. 2005 Dec. 8: 306(1-2): 99-106. Distribution of liposomal breviscapine in brain following intravenous injection in rats. Lv W I, Guo J, Li J, Huang L, Ping Q.). When scutellarin aglycone was orally administered at a dose of 200 mg/kg, both scutellarin aglycone and scutellarin could be detected in rat plasma, while when scutellarin aglycone was orally administered at a dose of 20 mg/kg, only scutellarin was detected, and no crude drug was detected (Che Qingming, Chen Ying, Pan Liyi, He Hong, Study on bile excretion of scutellarein [J], CHINA JOURNAL OF CHINESE MATERIA MEDICA, 2006, 20: 1710-1712.). Ju Wenzheng et al. determined the blood concentration and the clinical pharmacokinetics of scutellarin; 360 mg scutellarin was orally administered to a subject, and blood was collected at 1, 3, 5, 8 h to determine the concentration of scutellarin: 20 ng/mL of scutellarin was determined only at 5 h, while a large amount of scutellarin aglycone was detected in plasma and urine, suggesting that scutellarin might be hydrolyzed to scutellarin aglycone in colon and then absorbed (Ju Wenzheng, Chu Jihong, Tan Renxiang, Xiang Ningning, Study on metabolites of scutellarin in gastrointestinal tract by UPLC-MS/MS method [J]. CHINESE JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS, 2006, 03: 292-295.).
Due to the poor oral absorption of scutellarin, the oral availability is low. However, scutellarin aglycone can be converted to scutellarin in vivo, and is superior to scutellarin in terms of oral absorption. If scutellarin aglycone can be obtained in its stable crystal forms, it will be more favorable for drug development and industrial production.